This is a continuing study in the canine model of total body irradiation, marrow transplantation, methods of support for animals that have no bone marrow function and immunologic problems after marrow transplantation. The clinical marrow transplant protocols used in Seattle, and now being widely used in other medical centers, are to a considerable extent based on the results of past research supported by this grant. The major areas of proposed research to be conducted under the renewed grant are as follows: 1) prevention and treatment of graft-versus-host disease as the principal obstacle to a wide application of marrow transplantation to human disease. 2) Studies of "supralethal" fractionated total body irradiation designed to define the toxicity and immunosuppressive properties of fractionated irradiation with the objective of developing regimens that can be used to improve the cure rate of patients with acute leukemia. 3) To study the problem of resistance to hematopoietic grafts designed to overcome such resistance and improve the long-term success rate when donor-recipient pairs are not fully matched for the major histocompatibility complex. 4) To study lymphocyte-marrow interactions in vitro and in vivo in order to improve the success of marrow transplantation and also to provide information regarding graft-versus-host disease and stable graft-host tolerance.